RESUMO
The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c) signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d) and atorvastatin (15 mg/kg/d) via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL) for 8 weeks. Xyloketal B significantly improved HFD+HFL-induced hepatic histological lesions and attenuated lipid and glucose accumulation in the blood as well as lipid accumulation in the liver. Xyloketal B increased the expression of CPT1A, and decreased the expression of SREBP-1c and its downstream targeting enzymes such as ACC1, ACL, and FAS. Xyloketal B also significantly reduced lipid accumulation in HepG2 cells treated with free fatty acids (FFAs). These data suggested that xyloketal B has lipid-lowering effects via the SREBP-1c pathway that regulate lipid metabolism. Thus, targeting SREBP-1c activation with xyloketal B may be a promising novel approach for NAFLD treatment.
Assuntos
Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Piranos/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Linhagem Celular Tumoral , Dieta Hiperlipídica/efeitos adversos , Frutose/metabolismo , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacosRESUMO
The cluster of microRNAs (miRNAs) in the DLK1-DIO3 genomic imprinted region contains several miRNAs that have a significant regulatory role in tumor proliferation and invasion. One of these miRNAs is miR-134-3p, and its expression changes significantly in human ovarian cancer stem cells (OCSCs) and in CD44-/CD133- ovarian cancer. The results of a luciferase assay showed that miR-134-3p silenced RAB27A by binding to the 3'-UTR of RAB27A mRNA. Overexpression of miR-134-3p in human OCSCs can not only inhibit the expression of RAB27A but also can effectively downregulate the expression of some tumor proliferation and invasion genes. Overexpression of miR-134-3p can not only inhibit the in vitro proliferation and cell cycle progression of human OCSCs but also can decrease the tumorigenicity in nude mice.